PROJECT SUMMARY Fatigue is nearly a universal experience in the aged population and a very common clinical complaint. More than 20% of the United States population suffers from fatigue, which accounts for 10-15 million doctor visits every year. Cognitive or mental fatigue due to continuous workload, insufficient sleep, or illness significantly reduces quality of life, impairs cognitive performance, and increases the risk of automobile and workplace errors and accidents, at a societal cost of billions of dollars annually. Older people suffer significantly more from fatigue symptoms than younger individuals, yet the neural correlates underlying fatigue and its countermeasures on brain function have rarely been studied and remain largely unknown. Using multimodal functional magnetic resonance imaging (fMRI), we have successfully examined the neural correlates of cognitive fatigue in healthy young and middle aged adults after prolonged mental workload. Our data demonstrate that cognitive fatigue may be associated with altered resting brain function in the default mode network (DMN), frontoparietal attention network, thalamus, and basal ganglia regions. However, given significant structural and functional brain changes in these networks during aging, it remains unknown if fatigue will affect the aged brain in the same manner. The proposed research will combine our established multimodal functional MRI approach and validated fatigue paradigm to examine the neural correlates of cognitive fatigue after continuous mental workload in N=40 older adults (age between 55-85 years). We also propose to evaluate the efficacy of bright light treatment, a low-cost, non-pharmacological, and noninvasive intervention for promoting alertness, as a potential countermeasure for restoring fatigued brain function and improving performance after prolonged cognitive workload in the elderly. This study will test the hypothesis that cognitive fatigue will be associated with reduced resting brain activity and connectivity in the DMN, thalamus, and frontoparietal network in older adults, while bright light treatment will reduce fatigue symptoms by mitigating the brain function changes in these networks. The new knowledge gained from this study will have relevance not only for optimizing human performance and promoting safety of elderly after continuous task requirement (e.g., in transportation, medical care, and security), but also for understanding and managing fatigue symptoms in various aging-related diseases (e.g., cancer, dementia, Parkinson's disease, stroke, and traumatic brain injury). The project also has the potential to yield brain-based biomarkers of fatigue that may be used to predict individual responses to continuous task requirement as well as responses to light treatment for reducing fatigue and improving performance.